Light-dependent activity of the antitumor antibiotics ravidomycin and desacetylravidomycin

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Abstract
The antitumor antibiotics ravidomycin and desacetylravidomycin were studied by the biochemical lambda prophage induction assay. In this assay, induction of the enzyme beta-galactosidase is measured as a specific indication of the ability of an agent to directly or indirectly damage DNA. Induction was observed only when these two antibiotics were irradiated with light in the presence of the indicator organism. Drug treated with light followed by incubation with the indicator organism in the dark did not cause induction. Light in both the near UV and visible wave length ranges activated these antibiotics; near UV and visible blue wavelengths were most effective, while 597-nm light was totally ineffective. The amount of induction caused by these drugs varied directly with the dosage of light provided. Bacterial growth inhibition, as well as cytotoxicity for a human colon carcinoma cell line, was also dramatically enhanced by light. These data suggest that ravidomycin and desacetylravidomycin are potent photosensitizing, DNA-damaging agents.